IL-22 FC compositions

Abstract

The invention relates to compositions (e.g., pharmaceutical compositions) that include, for example, IL-22 Fc fusion proteins, methods of making the same, and methods of using the same, e.g., for the treatment of diseases (e.g., IBD).

What is claimed is: 
     
       1. A pharmaceutical composition comprising an IL-22 Fc fusion protein and a carrier, the IL-22 Fc fusion protein comprising an IL-22 polypeptide linked to an Fc region by a linker, wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO: 4, wherein the pharmaceutical composition comprises about 1 mg/mL to about 10 mg/mL IL-22 Fc fusion protein, about 5 mM methionine, about 10 mM sodium phosphate, about 240 mM sucrose, and about 0.02% (w/v) polysorbate 20, and wherein the pharmaceutical composition has a pH of about 7.1. 
     
     
       2. The pharmaceutical composition of  claim 1 , wherein the sodium phosphate comprises a mixture of sodium phosphate dibasic and sodium phosphate monobasic. 
     
     
       3. The pharmaceutical composition of  claim 1 , wherein the IL-22 Fc fusion protein has one or more properties selected from the group consisting of:
 (i) the IL-22 polypeptide is glycosylated; 
 (ii) the Fc region is not glycosylated; 
 (iii) the amino acid residue at position 297 as in the EU index of the Fc region is Gly or Ala or the amino acid residue at position 299 as in the EU index of the Fc region is Ala, Gly, or Val; 
 (iv) the Fc region comprises the CH2 and CH3 domain of IgG1 or IgG4; 
 (v) the IL-22 Fc fusion protein comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:8; and 
 (vi) the IL-22 Fc fusion protein comprises or consists of the amino acid sequence of SEQ ID NO:8, SEQ ID NO:10, or SEQ ID NO:16. 
 
     
     
       4. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises about 1 mg/mL IL-22 Fc fusion protein. 
     
     
       5. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises about 10 mg/mL IL-22 Fc fusion protein. 
     
     
       6. The pharmaceutical composition of  claim 1 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:8. 
     
     
       7. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is in a unit dosage form. 
     
     
       8. The pharmaceutical composition of  claim 1 , wherein the carrier is water. 
     
     
       9. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is stable:
 (a) through one or more freeze-thaw cycles; 
 (b) for about 2 weeks to about 52 weeks at about 25° C.; and/or 
 (c) for about 48 months to about 100 months at −20° C. 
 
     
     
       10. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition has a purity of about 85% to about 100% as assessed by size-exclusion high-performance liquid chromatography (SE-HPLC). 
     
     
       11. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition has a purity of about 75% to about 100% as assessed by nonreduced (NR) capillary electrophoresis sodium dodecyl sulfate non-gel sieving (CE-SDS-NGS). 
     
     
       12. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for intravenous, subcutaneous, intraperitoneal, or topical administration. 
     
     
       13. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition does not contain a preservative. 
     
     
       14. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for administration by infusion after dilution with an isotonic sodium chloride solution and/or a diluent. 
     
     
       15. The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition further comprises an additional therapeutic agent and/or a gelling agent. 
     
     
       16. A pharmaceutical composition comprising an IL-22 Fc fusion protein and a carrier, the IL-22 Fc fusion protein comprising the amino acid sequence of SEQ ID NO:8, wherein the pharmaceutical composition comprises about 10 mM sodium phosphate, about 240 mM sucrose, about 5 mM methionine, and about 0.02% (w/v) polysorbate 20, final concentration; and wherein the pharmaceutical composition has a pH of about 6.5 to about 8. 
     
     
       17. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition has a pH of about 6.6 to about 7.5. 
     
     
       18. The pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition has a pH of about 6.7 to about 7.4. 
     
     
       19. The pharmaceutical composition of  claim 18 , wherein the pharmaceutical composition has a pH of about 7 to about 7.1. 
     
     
       20. The pharmaceutical composition of  claim 16 , wherein the sodium phosphate comprises a mixture of sodium phosphate dibasic and sodium phosphate monobasic. 
     
     
       21. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition comprises about 1 mg/mL to about 10 mg/mL IL-22 Fc fusion protein. 
     
     
       22. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition is in a unit dosage form. 
     
     
       23. The pharmaceutical composition of  claim 16 , wherein the carrier is water. 
     
     
       24. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition is stable:
 (a) through one or more freeze-thaw cycles; 
 (b) for about 2 weeks to about 52 weeks at about 25° C.; and/or 
 (c) for about 48 months to about 100 months at −20° C. 
 
     
     
       25. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition has a purity of about 85% to about 100% as assessed by size-exclusion high-performance liquid chromatography (SE-HPLC). 
     
     
       26. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition has a purity of about 75% to about 100% as assessed by nonreduced (NR) capillary electrophoresis sodium dodecyl sulfate non-gel sieving (CE-SDS-NGS). 
     
     
       27. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition is formulated for intravenous, subcutaneous, intraperitoneal, or topical administration. 
     
     
       28. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition does not contain a preservative. 
     
     
       29. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition is formulated for administration by infusion after dilution with an isotonic sodium chloride solution and/or a diluent. 
     
     
       30. The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition further comprises an additional therapeutic agent and/or a gelling agent.